Clinical Translation of Memory Reconsolidation Research:

Bruce Ecker

Abstract

After 20 years of laboratory study of memory reconsolidation, the translation of research findings into clinical application has recently been the topic of a rapidly growing number of review articles. The present article identifies previously unrecognized possibilities for effective clinical translation by examining research findings from the experience-oriented viewpoint of the clinician. It is well established that destabilization of a target learning and its erasure (robust functional disappearance) by behavioral updating are experience-driven processes. By interpreting the research in terms of internal experiences required by the brain, rather than in terms of external laboratory procedures, a clinical methodology of updating and erasure unambiguously emerges, with promising properties: It is applicable for any symptom generated by emotional learning and memory, it is readily adapted to the unique target material of each therapy client, and it has extensive corroboration in existing clinical literature, including cessation of a wide range of symptoms and verification of erasure using the same markers relied upon by laboratory researchers. Two case vignettes illustrate clinical implementation and show erasure of lifelong, complex, intense emotional learnings and full, lasting cessation of major long-term symptoms. The experience-oriented framework also provides a new interpretation of the laboratory erasure procedure known as post-retrieval extinction, indicating limited clinical applicability and explaining for the first time why, even with reversal of the protocol (post-extinction retrieval), reconsolidation and erasure still occur. Also discussed are significant ramifications for the clinical field’s “corrective experiences” paradigm, for psychotherapy integration, and for establishing that specific factors can produce extreme therapeutic effectiveness.

1. Introduction
A primary dilemma in clinical psychology has been described by one of that field’s leading voices in this way: “After decades of psychotherapy research, we cannot provide an evidence-based explanation for how or why even our most well studied interventions produce change, that is, the mechanism(s) through which treatments operate” (Kazdin, 2007, p. 1). The present article proposes that a fundamental breakthrough in that dilemma may be developing through the translation of memory reconsolidation neuroscience into clinical application.

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Memory research has identified an innate type of neuroplasticity in the brain, known as memory reconsolidation, that can destabilize the neural encoding of learnings of many types, including emotional learnings. Destabilization in turn allows the target learning to be nullified either endogenously, by behavioral counter-learning, or exogenously, by pharmacological blockade that disrupts the natural molecular and cellular process of restabilization, or reconsolidation, that normally would occur after several hours (Duvarci and Nader, 2004; Pedreira et al., 2002; Pedreira and Maldonado, 2003; Walker et al., 2003). Thus nullified, the subsequent durable, robust disappearance of all expressions of the target learning has been termed its erasure by many researchers (e.g., Kindt et al., 2009; for reviews see, e.g., Agren, 2014; Nader, 2015; Reichelt and Lee, 2013; Schwabe et al., 2014; for a review of early, anomalous observations of erasure prior to discovery of reconsolidation, see Riccio et al., 2006). By putting the transformational change of memory on empirical solid ground, research on memory reconsolidation has paved the way for new common ground between neuroscientists and clinicians, who have filed fine-grained anecdotal reports of such transformational change for decades (e.g., Ecker and Hulley, 1996, 2000a, 2008; Fosha, 2000; Greenberg et al., 1993; Shapiro, 2001).

Memory reconsolidation is a neurological process that is experience-driven: behavioral and perceptual events trigger it into occurring and can govern the resulting effects on the target learning. The relevance of reconsolidation research findings to psychotherapy is potentially very great because clinical symptoms are maintained by emotional learnings held in implicit memory, outside of conscious, explicit awareness, in a wide range of cases, including most instances of insecure attachment, post-traumatic symptomology, compulsive behavior, addiction, depression, anxiety, low self-esteem, and perfectionism, among many other symptoms (e.g., Greenberg 2012; Schore, 2003; Toomey and Ecker, 2007; Van der Kolk, 1994). A versatile, reconsolidation-based clinical methodology that targets and reliably nullifies the specific emotional learnings maintaining such symptoms would revolutionize the field of psychotherapy. Envisioning that new landscape, neuroscientists Clem and Schiller (2016, p. 340) wrote, “To achieve greatest efficacy, therapies…should preclude the re-emergence of emotional responses.” Defining complete elimination of unwanted emotional responses as the goal of psychotherapy is a statement that no neuroscientist would have ventured to make prior to 2000, before the discovery of memory reconsolidation. It is a goal now recognized as a possibility grounded in empirical research. That goal is the operational definition of erasure in this article: lasting, effortless, complete cessation, under all circumstances, of an unwanted behavior, state of mind, and/or somatic disturbance that had occurred either continuously or in response to certain contexts or cues.

Currently, at the end of the second decade of laboratory research into reconsolidation, researchers’ attention is extending to considerations of clinical translation at a rapidly accelerating pace (e.g., Beckers and Kindt, 2017; Dunbar and Taylor, 2016; Elsey and Kindt, 2017a; Krawczyk et al., 2017; Kroes et al., 2015; Lee et al., 2017; Nader et al., 2014; Treanor et al., 2017). Those authors have consistently called for a two-way flow of knowledge between researchers and clinicians in order to achieve the fullest clinical utilization of memory reconsolidation. Nader et al. (2014, p. 475) wrote:

We feel that ongoing discourse between mental health clinicians and neuroscientists is beneficial both for scientific progress in neuroscience and mental health treatments. Neuroscientists may benefit from being educated about clinical models of mental disorders…. The reductionist approach intrinsic to scientific activity forces neuroscientists to simplify their models in the pursuit of scientific questions considered to be of a fundamental nature. Unavoidably, at times, this approach may ignore some aspects of mental disorders. A discourse with clinicians allows neuroscientists to realign their models to ensure that they represent processes thought to cause or maintain these disorders.

Similarly, researchers Elsey and Kindt (2017a) opined that “Dialogue between researchers and clinicians must be maintained” (p. 114) and, in concluding an extensive review of the prospects for effective clinical application of reconsolidation research findings, commented, “there are significant limitations to experimental research, and ultimately only attempts at treatment can reveal the utility of a reconsolidation-based approach” (p. 115).

Those comments serve to define the purpose of the present article, which is a report from the clinical trenches of observations made in the course of directly applying the empirically identified, endogenous process of memory erasure. This article describes what appear to be encouraging advances. The author, a psychotherapist and former research physicist, has since 2005 maintained close scrutiny of reconsolidation research while also closely observing the effects in therapy sessions of processes designed to translate memory reconsolidation research into clinical application.

Members of the clinical domain have been enthusiastically consuming and working to utilize the knowledge being generated by laboratory neuroscience researchers since the 1990s (e.g., Siegel, 1999; van der Kolk, 1994). There has been little to indicate a flow of knowledge in the other direction, however. Undoubtedly there is more than one reason for that asymmetry, which is particularly acute at present as regards reconsolidation. There is now a substantial clinical literature that documents observations ascribed to reconsolidation and that delineates clinical methodologies demonstrating translation of reconsolidation research (e.g., Ecker, 2008, 2010, 2015a,b, 2016; Ecker and Hulley, 2008, 2017; Ecker and Toomey, 2008; Ecker et al., 2012, 2013a,b; Högberg et al., 2011; Lasser and Greenwald, 2015; Sibson and Ticic, 2014; Soeter and Kindt, 2015a; Ticic and Kushner, 2015). Rarely, however, is such literature cited in the writings of laboratory researchers, who regularly express anticipation of and need for advances already made by clinicians. Examples of that are myriad; the two most recent instances encountered by the author are these: Krawczyk et al. (2017, p. 16) commented that “outside the laboratory settings such as in clinical ones, it is unclear how the reconsolidation process might work.” Elsey and Kindt (2017a, p. 114) commented that laboratory research has focused largely on fear learnings and that “experiences of other emotions, such as disgust…or of more complex feelings such as guilt and shame after reconsolidation-based procedures are essentially untapped.” In fact, numerous clinicians’ reports have documented in a fine-grained manner how a wide range of complex emotions and emotional learnings have been subjected to the empirically confirmed reconsolidation process of behavioral erasure (see citations above in this paragraph; for online listings of relevant clinical reports, see http://bit.ly/2tKXdyX and http://bit.ly/15Z00HQ). Section 7 of this article provides samples of such clinical work and its documentation.

The rigor of the clinical observations reported here is of a different type from that of the quantitative measurements made in laboratory controlled studies by neuroscientists. Here the aim is phenomenological rigor that capitalizes on the unique ability of human subjects (therapy clients) to direct attention to their own mental and emotional states and to describe the moment-to-moment effects as the steps of the destabilization and erasure process are carried out. Neuroscientists have barely begun to utilize such articulation of subjective experience for gaining access to the memory reconsolidation process, but even their first forays in that direction were very fruitful (Sevenster et al., 2013, 2014). The clinical case studies documented in this article are intended to show that examining the raw data of therapy clients’ real-time phenomenological reports can significantly help advance the clinical translation of memory reconsolidation research (see also Heatherington et al., 2012).

The clinical work reported here is intended to demonstrate the application of reconsolidation research, so an examination of relevant research and its translational implications precedes the clinical material detailed in Section 7. As noted, reconsolidation has been demonstrated and studied for many different types of memory, but the research covered here is limited to how the process applies to emotional learning and emotional memory, as they play by far the principal role in psychotherapy. (See reviews cited above for the full range of research.) The cellular and molecular levels of reconsolidation research are also not covered here. Clinicians need not attend to the highly complex neurophysiological and neurochemical substrates of destabilization and erasure (for a review of which, see Clem and Schiller, 2016). However, clinicians should understand that robust functional erasure does not necessarily correspond to total loss or ablation of the entire neural encoding of the erased responses and learnings, according to recent findings (Ryan et al., 2015), and any simplistic image of what happens to neural circuits when erasure is achieved is almost certain to be significantly incorrect.

Lastly, regarding this article’s usage of an emotional “learning”: A terminology bridge between neuroscientists and clinicians is much needed. Memory researchers as a rule refer to a learned item of any type as a “memory,” not as a “learning”; they refer to the “target memory” rather than the “target learning.” If the learned item in question is, for example, implicit knowledge that would be verbalized as “If I express myself I’ll be criticized and rejected,” researchers would refer to that as the “memory” under study. That usage of “memory,” while perfectly clear to memory researchers, is likely (in the author’s experience) to create considerable confusion for clinicians, who would tend to understand “memory” as referring to the person’s episodic memory and/or declarative memory of the original childhood events involving rejection, rather than the semantic memory consisting of a generalized model and expectation of people being active rejecters. In order to avoid that confusion for clinician readers (this article being intended for both memory researchers and clinicians), the text here refers to an “emotional learning.” That syntax is identical to how “understanding” may be used as in “it resulted in the understanding that….”